Calcium signalling in cardiac muscle: refractoriness revealed by coherent activation

Contraction of cardiac myocytes is governed by calcium-ion (Ca2+)-induced C a2+ release (CICR) from the sarcoplasmic reticulum through Ca2+-release cha nnels. Ca2+ release occurs by concerted activation of numerous elementary C a2+ events,'Ca2+ sparks', that are triggered and locally, controlled by Ca2 + influx into the cell through plasmalemmal L-type Ca2+ channels. Because o f the positive feedback inherent in CICR, an as-yet-unidentified control me chanism is required to restrain the amplification of Ca2+ signalling and to terminate Ca2+ release from the sarcoplasmic reticulum, Here we use ultrav iolet-laser flash and two-photon photolysis of caged Ca2+ to study spatiote mporal features of the termination and refractoriness of Ca2+ release, Cohe rent and simultaneous activation of all Ca2+-release sites within a cardiac myocyte unmasked a prominent refractoriness, recovering monotonically with in about 1 second. In contrast, selective activation of a few Ca2+-release sites was not followed by a refractoriness of Ca2+ release from the sarcopl asmic reticulum. This discrepancy is consistent with the idea that a functi onal depletion of Ca2+ from the cellular sarcoplasmic-reticulum network may underlie the refractoriness of CICR observed after a whole-cell Ca2+ trans ient. These results also imply the requirement for further mechanisms to te rminate spatially limited subcellular Ca2+-release events such as Ca2+ spar ks.